The mobilization of free fatty acids from adipose tissue is catalyzed by hormone-sensitive lipase and failure to regulate this enzyme accounts for many of the pathophysiologic accompaniments of diabetic ketoacidosis. Recent progress in the purification of this enzyme now makes it possible to carry out meaningful studies of the detailed molecular structure of the enzyme protein, the relationship of the several hydrolase activities that are closely associated with each other in crude preparations and the nature of the molecular changes accompanying activation by cyclic AMP-dependent protein kinase. Adipose tissue contains a high level of neutral cholesterol esterase which is activated by protein kinase. Studies are under way to determine whether this enzyme plays its role in the mobilization of stored cholesterol esters, in the hydrolysis of cholesterol esters taken up with lipoproteins or both. It has recently been shown that adipose tissue is one of the tissues playing a significant role in the catabolism of low density lipoprotein in vivo. Using 3T3-L1 cells, which assume many of the properties of differentiated adipose tissue under proper conditions, and using freshly isolated adipocytes, studies will be undertaken to characterize the high-affinity LDL receptor mechanism in adipose tissue and its regulation. Low-affinity mechanisms will also be studied, particularly in relation to the possible role of adipose tissue cholesterol esterase. Finally, using a technique recently developed in this laboratory, attempts will be made to determine whether the diabetic state influences rates of LDL degradation and sites of LDL degradation in vivo. Special attention will be paid to the rates of uptake in arterial wall, since an abnormality here could contribute to the premature atherosclerosis associated with diabetes even in the absence of hyperlipoproteinemia.